Human performance is not a constant. We all have good days and bad days, times when we work or act efficiently and times when we are inefficient. Motivation has often been studied by changing the amount or the waiting time for reward, but the effect of internal fluctuations of motivation has never been studied in the frontal and parietal cortex of the monkey. Preliminary results from this laboratory indicate that the monkey lateral intraparietal area (LIP) has a signal which, rather than describing what the monkey sees or will do, correlates with the monkey's probability of success on the current trial of a difficult task, and therefore fits the criteria for an arousal or motivational signal rather thana sensoriomotor signal. This signal may be the cortical manifestation of ascending pathways, and if so it should be found in other visual and oculomotor areas, and should have pharmacological properties related to modulatory as opposed to sensorimotor processing. In a difficult visual search task, which begins with the monkey looking at a fixation spot for 500 ms before the search array appears, the baseline activity of neurons in LIP during the fixation period predicts both the monkey's probability of success or failure in the task, and the intensity of the transient visual response to the array onset. The baseline activity correlates inversely, on a trial-by-trial basis, with a recency-weighted index of the monkey's history of success or failure, increasing when the monkey has recently has done poorly and decreasing when the monkey has done well. The baseline does not predict the location of the target in the impending array, and it is unrelated to the monkey's locus of spatial attention as determined by the monkey's response in a cued visual reaction time task. The first aim of this proposal is to verify this signal in LIP, ad then see if it exists in two other visual areas, the frontal eye field (FEF) and prestriate area V4 Further evidence for a behaviorally relevant, spatially non-specific signal in LIP comes from studying noise correlation in a foraging task. Neurons that do not share excitatory receptive fields nonetheless exhibit significant noise correlation, which is maximal during the pretarget fixation period, and also varies inversely with the monkey's history of success and failure. The second aim of this proposal is to verify these findings in the search task and extend them to FEF and V4. The hallmark of a modulatory signal is that it should be modifiable by neurotransmitters associated with ascending pathways. Acetylcholine (ACh) increases the baseline and visual transient signals in LIP, and mecamylamine, an ACh nicotinic receptor antagonist, suppresses the signals, suggesting that nicotinic cholinergic signals are important in modulating sensorimotor activity in LIP. The third aim is to verify these results in LIP, and extend them to FEF and V4. Most behaviorally relevant drugs work on modulatory systems. Understanding the mechanism by which modulatory systems affect visual processing is critical to understanding the mechanism of action of these drugs, and will facilitate the design of new and better agents.